Biopolym. Cell. 2011; 27(5):390-393.
http://dx.doi.org/10.7124/bc.00012B
Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells
1, 2Massade L.
  1. Universite Paris-Sud, CNRS, UMR 8203, Orsay
    Orsay, France, F-91405
  2. Institut Gustave Roussy
    114, rue Edouard Vaillant, Villejuif, France, 94805

Abstract

RET/PTC1 fusion oncogene is the most common genetic alteration identified to date in thyroid papillary carcinomas (PTC) and represents a good target for small interfering RNA (siRNA). Our aim was: i) to target the RET/PTC1 oncogene by siRNAs, ii) to assess the knockdown effects on cell growth and cell cycle regulation and iii) to vectorize it in order to protect it from degradation. Methods. Human cell lines expressing RET/PTC1 were transfected by siRNA RET/PTC1, inhibition of the oncogene expression was assessed by qRT-PCR and by Western blot. Conjugation of siRNA RET/PTC1 to squalene was performed by coupling it to squalene. In vivo studies are performed in nude mice. Conclusion. In this short communication, we report the main published results obtained during last years.
Keywords: RET/PTC1, siRNA, thyroid papillary carcinomas
Full text: (PDF, in English)

References

[1] Nambiar M., Kari V., Raghavan S. C. Chromosomal translocations in cancer Biochim. Biophys. Acta 2008 1786, N 2 P. 139–152.
[2] Teixeira M. R. Recurrent fusion oncogenes in carcinomas Crit. Rev. Oncog 2006 12, N 3–4 P. 257–271.
[3] Aman P. Fusion genes in solid tumors Semin. Cancer Biol 1999 9, N 4 P. 303–318.
[4] Jhiang S. M. The RET proto-oncogene in human cancers Oncogene 2000 19, N 49 P. 5590–5597.
[5] Di Cristofaro J., Vasko V., Savchenko V., Cherenko S., Larin A., Ringel M. D., Saji M., Marcy M., Henry J. F., Carayon P., De Micco C. ret/PTC1 and ret/PTC3 in thyroid tumors from Chernobyl liquidators: comparison with sporadic tumors from Ukrainian and French patients Endocr. Relat. Cancer 2005 12, N 1 P. 173–183.
[6] Nikiforov Y. E. Radiation-induced thyroid cancer: what we have learned from chernobyl Endocr. Pathol 2006 17, N 4 P. 307–317.
[7] Fusco A., Grieco M., Santoro M., Berlingieri M. T., Pilotti S., Pierotti M. A., Della Porta G., Vecchio G. A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases Nature 1987 328, N 6126 P. 170–172.
[8] Fusco A., Santoro M. 20 years of RET/PTC in thyroid cancer: clinico-pathological correlations Arq. Bras. Endocrinol. Metabol 2007 51, N 5 P. 731–735.
[9] Viglietto G., Chiappetta G., Martinez-Tello F. J., Fukunaga F. H., Tallini G., Rigopoulou D., Visconti R., Mastro A., Santoro M., Fusco A. RET/PTC oncogene activation is an early event in thyroid carcinogenesis Oncogene 1995 11, N 6 P. 1207–1210.
[10] Tallini G., Asa S. L. RET oncogene activation in papillary thyroid carcinoma Adv. Anat. Pathol 2001 8, N 6 P. 345–354.
[11] Santoro M., Melillo R. M., Fusco A. RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture Eur. J. Endocrinol 2006 155, N 5 P. 645– 653.
[12] Nikiforova M. N., Stringer J. R., Blough R., Medvedovic M., Fagin J. A., Nikiforov Y. E. Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells Science 2000 290, N 5489 P. 138–141.
[13] Nikiforov Y. E. RET/PTC rearrangement in thyroid tumors Endocr. Pathol 2002 13, N 1 P. 3–16.
[14] Chiappetta G., Toti P., Cetta F., Giuliano A., Pentimalli F., Amendola I., Lazzi S., Monaco M., Mazzuchelli L., Tosi P., Santoro M., Fusco A. The RET/PTC oncogene is frequently activated in oncocytic thyroid tumors (Hurthle cell adenomas and carcinomas), but not in oncocytic hyperplastic lesions J. Clin. Endocrinol. Metab 2002 87, N 1 P. 364–369.
[15] Brummelkamp T. R., Bernards R., Agami R. A system for stable expression of short interfering RNAs in mammalian cells Science 2002 296, N 5567 P. 550–553.
[16] Bertling W. M., Gareis M., Paspaleeva V., Zimmer A., Kreuter J., Nurnberg E., Harrer P. Use of liposomes, viral capsids, and nanoparticles as DNA carriers Biotechnol. Appl. Biochem 1991 13, N 3 P. 390–405.
[17] Couvreur P., Reddy L. H., Mangenot S., Poupaert J. H., Desmaele D., Lepetre-Mouelhi S., Pili B., Bourgaux C., Amenitsch H., Ollivon M. Discovery of new hexagonal supramolecular nanostructures formed by squalenoylation of an anticancer nucleoside analogue Small 2008 4, N 2 P. 247–253.
[18] Couvreur P., Stella B., Reddy L. H., Hillaireau H., Dubernet C., Desmaele D., Lepetre-Mouelhi S., Rocco F., DereuddreBosquet N., Clayette P., Rosilio V., Marsaud V., Renoir J. M., Cattel L. Squalenoyl nanomedicines as potential therapeutics Nano Lett 2006 6, N 11 P. 2544–2548.
[19] Gilbert-Sirieix M., Ripoche H., Malvy C., Massaad-Massade L. Effects of silencing RET/PTC1 junction oncogene in human papillary thyroid carcinoma cells Thyroid 2010 20, N 10 P. 1053–1065.
[20] Raouane M., Desmaele D., Gilbert-Sirieix M., Gueutin C., Zouhiri F., Bourgaux C., Lepeltier E., Gref R., Ben Salah R., Clayman G., Massaad-Massade L., Couvreur P. Synthesis, characterization, and in vivo delivery of siRNA-squalene nanoparticles targeting fusion oncogene in papillary thyroid carcinoma J. Med. Chem 2011 54, N 12 P. 4067–4076.